IMMOBILIZATION OF DOXORUBICIN ON THE OLYGOELECTROLYTIC POLYMERIC CARRIERA VEP-GMA-PEG INCREASES ITS AND ANTICANCER ACTIVITY CELLULAR UPTAKE
DOI: http://dx.doi.org/10.30970/sbi.0602.225
Abstract
Application of special systems for drug delivery into target cells might be useful for overcoming several problems in treatment of dangerous diseases. These are: consequences of nonspecific negative effects of drugs towards healthy cells, low sensitivity of cancer cells to anticancer drugs used in doses that are non-toxic for the organism, resistance of tumor cells to anticancer drugs and of the pathogenic microorganisms to the antibiotics. Here we studied the efficiency of application of novel nanoscale drug delivery system in tumor cell lines, including drug-resistant ones. The polyethylene glycol (PEG)-modified polymeric carrier VEP-GMA used in this study, was synthesized at the Department of Organic Chemistry of Lviv National Polytechnic University. We compared the effect of free doxorubicin and of this anticancer drug immobilized on the polymeric carrier, towards human tumor cells. It was found that such immobilization of doxorubicin significantly enhanced the cytotoxic action of this drug towards human lung carcinoma A549 cells, human colorectal carcinoma HCT116 cells, human breast carcinoma MCF-7 cells and their doxorubicin-resistant MCF-7/ADR subline. The results of our studies demonstrated that using doxorubicin complex with novel polymeric nanoscale carrier VEP-GMA-PEG permitted reducing the active dose of doxorubicin in cancer cells at least 10 times, comparing with such dose of this anticancer drug used in free form. Since the antineoplastic effect of carrier-immobilized doxorubicin was maintained, these results suggest a potential reduction of negative side effects of the corresponding chemotherapy. It was shown that the uptake by tumor cells of the carrier- immobilized doxorubicin was significantly enhanced comparing with such uptake of free doxorubicin. Our data demonstrated that neither macropinocytosis, nor endocytosis can be responsible for the uptake of doxorubicin that is immobilized on the nanosized polymeric carrier. Our future experiments are focused on the improvement of characteristics of this carrier by means of its specific functionalization aimed at reaching its addressed action towards tumor cells in vitro and in vivo.
Keywords
Full Text:
PDF (Українська)References
1. Bharali D.J., Khalil M., Gurbuz M. et al. Nanoparticles and cancer therapy: A concise review with emphasis on dendrimers. Int J Nanomedicine, 2009; 4: 1-7. | |
| |
2. Caruthers S.D., Wickline S.A., Lanza G.M. Nanotechnological applications in medicine. Curr. Opin. Biotechnol, 2007; 18: 26-30. | |
| |
3. Cerquaglia C., Diaco M., Nucera G. et al. Pharmacological and Clinical Basis of Treatment of Familial Mediterranean Fever (FMF) with Colchicine or Analogues: An Update. Current drug targets: inflammation and allergy, 2005; 4(1): 117-124. | |
| |
4. Clavinas H., Crajcsi P., Cserepes J., Sarcadi B. The role of ABC transporters in drug resistans, metabolism and toxicity. Current drug delivery, 2004; 1: 27-42. | |
| |
5. Dutta R.C. Drug carriers in pharmaceutical design: promises and progress. Curr. Pharm. Des, 2007; 13: 7, 761-769. | |
| |
6. Enari M., Sakahira H., Yokoyama H. et al. Caspase-activated DNase that degrades DNA. Nature, 1998; 391: 43-46. | |
| |
7. Euliss L.E., DuPont J.A., Gratton S., DeSimone J. Imparting size, shape, and composition control of materials for nanomedicine. Chem. Soc. Rev, 2006; 35: 1095-104. | |
| |
8. Geng F., Shen Y., Peng B. et al. Visualization and characterization of drug carrier transportation and distribution in vivo. Conf. Proc. IEEE Eng. Med. Biol. Soc., 2005; 1: 508-11. | |
| |
9. Han S., Liu Y., Nie X. et al. Efficient delivery of antitumor drug to the nuclei of tumor cells by amphiphilic biodegradable poly(L-aspartic acid-co-lactic acid)/DPPE co-polymer nanoparticles. Small, 2012; 8(10): 1596-606. | |
| |
10. Hoffman B., Lieberman P. Molecular controls of apoptosis: differentiation/growth arrest primary response genes, protooncogenes, and tumor suppressor genes as positive and negative modulators. Oncogene,1994; 9: 1807-11. | |
| |
11. Horák D., Shagotova T., Mitina N. et al. Surface-Initiated Polymerization of 2-Hydroxyethyl Methacrylate from Heterotelechelic Oligoperoxide-Coated γ-Fe2O3 Nanoparticles and their Engulfment by Mammalian Cells. Chem. Mater, 2011; 23(10): 2637-49. | |
| |
12. Ishikawa T., Kuo M.T., Furuta K., Suzuki M. The human multidrug resistance-associated protein (MRP) gene family: from biological function to drug molecular design. Clin Chem Lab Med, 2000; 38: 893-7. | |
| |
13. Mozafari M.R., Pardakhty A., Azarmi S. et al. Role of nanocarrier systems in cancer nanotherapy. Journal of Liposome Research, 2009; 19(4): 310-21. | |
| |
14. Magnarin M., Morelli M., Rosat A. et al. Induction of proteins involved in multidrug resistance (P-glycoprotein, MRP1, MRP2, LRP) and of CYP 3A4 by rifampicin in LLC-PK1 cells. Eur J Pharmacol, 2004; 483: 19-28. | |
| |
15. Manabe N., Hoshino A., Liang Y.Q. et al. Quantum dot as a drug tracer in vivo. IEEE Trans. Nanobioscience, 2006; 5(4): 263-7. | |
| |
16. Theodoropoulos P.A., Gravanis A., Tsapara A. et al. Cytochalasin B may shorten actin filaments by a mechanism independent of barbed end capping. Biochem. Рharmacol, 2009; 47(10): 1875-81. | |
| |
17. Vollrath V., Wielandt A.M., Iruretagoyena M., Chianale J. Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem J, 2006; 395: 599-609. | |
| |
18. Zaichenko A., Mitina N., Shevchuk O. et al. Oligoperoxide Based Physically Detectable Nanocomposites for Cell Targeting, Visualization and Treatment. AIP Conference Proceedings, 2010; 1275: 178-82. | |
| |
19. Рябцева А., Мітіна Н., Бойко Н. та ін. Синтез нових поліетиленглікольвмісних носіїв для доставки лікарських засобів. Праці наукового товариства ім. Шевченка. Хемія і Біохемія, 2011; 28: 19-27. | |
Refbacks
- There are currently no refbacks.
Copyright (c) 2012 Studia biologica
This work is licensed under a Creative Commons Attribution 4.0 International License.